DHEA, Estrogen, & Testosterone

Each of these hormones has been found helpful for depression in some middle-aged individuals.  Each has a concern about cancer risks.  DHEA and testosterone have their own pages.  I might first try a carnitine, which might obtain most or all of the same benefits without the cancer risk.

Estrogen (estradiol) is beneficial in both treating post-partum depression and in preventing its recurrence is women with a past episode. Post-partum depression occurs due to the dramatic decreases in female hormone levels shortly after delivery. During pregnancy, hormone levels climb dramatically. The crash back down to normal levels causes a few days of depressed feelings in many women. Severe depression and even psychosis occurs in some women.

Estradiol is reported to be of value in treating women ages 40-60 for dysthymia or major depression in two recent studies from Harvard and from the National Institute of Mental Health. There is even one study finding some benefit of estrogen as a adjunct to an SSRI, although this study needs to be replicated to assure that it was not just a chance finding.

Unfortunately, for both DHEA and estradiol, there is a real concern that these supplements could increase breast cancer in women, especially obese post-menopausal women. Women who naturally have higher levels of both of these hormones have higher rates of breast cancer. One treatment for advanced breast cancer tries to block the effects of naturally occurring DHEA. While there is some evidence of DHEA decreasing breast cancer, the clear majority of the evidence is in the other direction. For men, the concern is on prostate cancer.

HRT Decreases DHEA & Testosterone in Most Menopausal: Menopausal ERT decreases serum androgen levels, decreasing DHEA-sulfate and testosterone by 23% and 42%, respectively. Whereas the decline in testosterone is likely due to decreased LH-driven ovarian stromal steroidogenesis, the declining levels of DHEA-sulfate also may imply a direct adrenal effect of estrogen. Effect of postmenopausal estrogen replacement on circulating androgens. Casson PR, Elkind-Hirsch KE, Buster JE, Hornsby PJ, Carson SA, Snabes MC. Obstet Gynecol 1997 Dec;90(6):995-8

Estrogen Patch Helps Post-Partum Depression: Women with major depression within 3 mo of delivery Rx DB PC study with estrogen patch. England, Lancet ’96;347:930

Post-Partum Depression Prevented by Estrogen: Prophylactic estrogen in recurrent postpartum affective disorder. Biol Psych 95;38:814

Postpartum Psychosis Rx Estradiol: 10 Finnish with psychosis emerging average of 12 days post-partum referred after 73 days of symptoms. Several had progressed to florid psychosis over many months. 4 had neuroleptics. Serum estrdiol at baseline 14 pg/mL (reference range 30-400). Rx 6 weeeks sublingual 17 Beta-estradiol, 1 mg 3-6 times per day (mean 4.7) to target blood level of 109 pg/ml (1/3 of normal peak during menstrual cycle). Patients symptoms gone by end of week 2. Ahokas, J Clin Psych 00;61:166

Estradiol Patch Helps Perimenopausal in DB: Transdermal patches of 17beta-estradiol (100 microgram) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomery-Asberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scores. RESULTS: Fifty women 40-55yo with FSH>25 and irreg periods were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17beta-estradiol compared with 5 (20%) in the placebo. MGH, Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Soares CN, Almeida OP, Joffe H, Cohen LS., Arch Gen Psychiatry 2001 Jun;58(6):529-34

Estradiol Helps Perimenopausal in DB: 34 female subjects, 16 received estradiol first and 18 received placebo first. After 3 weeks of estradiol, standardized mood rating scale scores and visual analog scale symptom scores (eg, sadness, anhedonia, and social isolation) were significantly decreased compared with baseline scores (P <.01) and were significantly lower than scores in women receiving placebo (P <.01), who showed no significant improvement. Neither the presence of hot flushes nor the duration of treatment (3 weeks vs 6 weeks) influenced outcome. A full or partial therapeutic response was seen in 80% of subjects receiving estradiol and 22% of those receiving placebo. NIMH, Estrogen replacement in perimenopause-related depression: a preliminary report. Schmidt PJ, Nieman L, Danaceau MA, Tobin MB, Roca CA, Murphy JH, Rubinow DR., Am J Obstet Gynecol 2000 Aug;183(2):414-20

Estrogen Increases Benefit of Sertraline: 34 sertraline-treated depressed women on estrogen replacement therapy did better than 93 without ERT in 12 week, DB with 79% vs. 58% much improved. 9 pt on both ERT and medroxyprogesterone were excluded. Lon Schneider, USC, APA 5/30/98

Estrogen Increased Benefit of Fluoxetine in Peri-Menopausal: In a very small randomized study, those treated with an estradiol patch (0.1-0.2 mg) plus fluoxetine (10-20 mg/d) did best, followed by fluoxetine alone, and then by estrogen patch alone. UCSD. Does estrogen enhance the antidepressant effects of fluoxetine? Westlund Tam L, Parry BL. J Affect Disord. 2003 Oct;77(1):87-92

Hypogonadism & Depression Helped by Hormone: Burris, J Andrology 92;13:297; Also for hypogonadal men with SSRI refractory depression. J Aff Disorder 98;48:157

Testosterone No Benefit Depression: DB PC 30 men hypogonadal + MDD 6 wk. Testosterone enanthate 1 cc /wk. in 13. Clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo. Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. Seidman SN, Spatz E, Rizzo C, Roose SP. J Clin Psychiatry 2001 Jun;62(6):406-12

Testosterone Helps Sex and Depression in Oopharectomized Women: DB PC 75 31-56yos. The ovaries provide approximately half the circulating testosterone in premenopausal women. All on estrogen 0.625/d. 300microg/d testosterone via patch was higher dose. At the higher dose the percentages of women who had sexual fantasies, masturbated, or engaged in sexual intercourse at least once a week increased two to three times from base line. The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose (P=0.04, P=0.03, and P=0.04, respectively, for the comparison with placebo), but the scores on the telephone-based diary did not increase significantly. CONCLUSIONS: In women who have undergone oophorectomy and hysterectomy, transdermal testosterone improves sexual function and psychological well-being. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, Burki RE, Ginsburg ES, Rosen RC, Leiblum SR, Caramelli KE, Mazer NA.

Testosterone Improves Mood & Sex in Hypogonodal Men: T gel replacement improved sexual function and mood, increased lean mass and muscle strength (principally in the legs), and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch. 227 pt 6 months rx. UCLA, Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group. Wang C, Swedloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N. J Clin Endocrinol Metab 2000 Aug;85(8):2839-53

Testosterone Improves Libido, Mood in HIV+: 6 wk DB PC with 12 more open. Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness, restoring libido and energy, alleviating depressed mood, and increasing muscle mass. (Why increase libido in these men?). Testosterone biweekly injections. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Rabkin JG, Wagner GJ, Rabkin R., Arch Gen Psychiatry 2000 Feb;57(2):141-7; discussion 155-6, Columbia U

Testosterone > SSRIs for HIV+: Says their clinical trials show 72% response rate imipramine and 81% response rate with testosterone. A comparative analysis of standard and alternative antidepressants in the treatment of human immunodeficiency virus patients. Wagner GJ, Rabkin JG, Rabkin R., Compr Psychiatry 1996 Nov-Dec;37(6):402-8. HIV patients apparently often low in testosterone.

Very High Testosterone Causes Manic Symptoms in Some: Testosterone administration, 600 mg/wk increased ratings of manic symptoms in normal men. This effect, however, was not uniform across individuals; most showed little psychological change, whereas a few developed prominent effects. 600mg/wk with testosterone cyprionate. DBPC 56 men 20-50yo. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial. McLean. Pope HG Jr, Kouri EM, Hudson JI., Arch Gen Psychiatry 2000 Feb;57(2):133-40; discussion 155-6

Thomas E. Radecki, M.D., J.D.

 modern-psychiatry.com